Older men screened for the presence of cardiovascular and metabolic disease prior to entry into exercise training and/or weight loss intervention were found to have a 25% incidence of silent myocardial ischemia (SI). A reduction in HDLC and HD1/2 subspecies was found, independent of the % body fat or V02 max of the subjects. An equivalent percentage of athletes and obese sedentary individuals were found to have SI, and the metabolic abnormalities in both groups were comparable except for a greater reduction in HDL-C in the obese sedentary individuals. Plasma HDL-C and the HDL2 subspecies were low in the individuals with SI. Gradient gel electrophoresis revealed an increase in the HD3a and 3c subspecies and reciprocal declines in the HDL2b subspecies which correlated inversely with hepatic lipase activity. Individuals with low HD1/2-C levels had high hepatic activity, independent of body composition or V02max. Individuals with SI consistently had higher hepatic lipase and lower HDL2 subspecies levels than their nonischemic controls. An ApoE 4,3 phenotype was more prevalent in the individuals with SI than in the normal controls. Whether or not the ApoE 4,3 phenotype represents a genetic form of dyslipoproteinemia is unclear, and family studies are planned to test this possibility. In addition, the individuals with SI tended to have a higher WHR than the nonischemic controls, suggesting that the regional distribution of body fat may be an important determinant of risk for silent myocardial ischemia and low HDL-C. Studies are in progress to examine the relationship of a high waist to hip ratio to HDL-C, hepatic lipase activity and plasma lipoprotein lipid levels. Sex hormone binding globulin levels will be measured and related to levels of insulin sensitivity, VO2max, and WHR in these subjects. These studies represent collaborative efforts of scientists in the Metabolism Section, LCP, GRC, NIA and members of the Geriatrics Division, Johns Hopkins University at the Francis Scott Key Medical Center.